PROJECT SUMMARY The overall goal of our Digestive Health Center (DHC): Bench-to-Bedside Research in Pediatric Digestive Disease is to promote research that will yield insights into the fundamental processes and pathogenic mechanisms of digestive disease in children and generate innovative treatment to restore digestive health. The second award period of the DHC was very successful, with Core services that evolved to meet the scientific needs of innovative investigators, a strong Research Base of 83 investigators and $30.5 million of extramural digestive disease-related funds, Pilot and Feasibility (P/F) Awardees that transitioned to R01-funded investigators, and a dynamic enrichment series. This trajectory of success will be pursued in future years by fostering research and promoting interdivisional and interdepartmental collaboration to maintain a solid critical mass in digestive disease research, with a focus on translational research. Specifically, our long term goals are to improve child health through better diagnosis, treatments and outcomes that will emerge from highly innovative work in our four key focus areas: 1) Liver disease modeling, 2) Digestive disease and immunity, 3) Digestive disease and obesity, and 4) Translational embryology. Each focus area brings opportunities for potential impact on the digestive health of children, helps advance the national research agenda, and creates a unique environment to integrate research into patient care. The focus areas are linked by three complementary and uniquely innovative Biomedical Research Cores (Gene Analysis Core, Integrative Morphology Core, and Pluripotent Stem Cell and Organoid Core) and by a Clinical Component of the Administrative Core to facilitate patient-based research. Collectively they form a powerful infrastructure that fosters the development of personalized and predictive medical approaches based on the genetics and molecular basis of GI disorders, and of therapies that take into account basic mechanisms of disease. Our working model promotes laboratory discoveries to generate translational research opportunities that lead to validation in patient samples and is followed by clinical trials. To strengthen pediatric digestive disease, the DHC will foster collaboration among its investigators and investigators from other disciplines. It will also fund highly promising P/F Projects for junior investigators and will sponsor a dynamic enrichment program of scientific seminars, workshops and symposia. With these strategies and an exceptionally supportive institution, the DHC is well positioned to catalyze translational research in pediatric digestive disease.